Anti-PD-L1 antibodies and uses thereof

Abstract

Provided are anti-PD-L1 antibodies or fragments thereof. The antibodies or fragments thereof specifically bind to the immunoglobulin C domain of the PD-L1 protein. In various example, the antibodies or fragments thereof include a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 2, a VH CDR3 of SEQ ID NO: 3, a VL CDR1 of SEQ ID NO: 4, a VL CDR2 of SEQ ID NO: 5, and a VL CDR3 of SEQ ID NO: 6, or variants of each thereof. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer and infectious diseases are also provided.

What is claimed is: 
     
       1. A method of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of an antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human Programmed death-ligand 1 (PD-L1) protein and comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 2, a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 3, a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 6. 
     
     
       2. The method of  claim 1 , wherein the cancer is selected from the group consisting of bladder cancer, liver cancer, colon cancer, rectal cancer, endometrial cancer, leukemia, lymphoma, pancreatic cancer, small cell lung cancer, non-small cell lung cancer, breast cancer, urethral cancer, head and neck cancer, gastrointestinal cancer, stomach cancer, oesophageal cancer, ovarian cancer, renal cancer, melanoma, prostate cancer and thyroid cancer. 
     
     
       3. A method of treating cancer in a patient in need thereof, comprising:
 (a) treating a T cell, in vitro, with an antibody or fragment thereof; and 
 (b) administering the treated T cell to the patient, 
 wherein the antibody or fragment thereof has specificity to a human Programmed death-ligand 1 (PD-L1) protein and comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 2, a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 3, a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 6. 
 
     
     
       4. The method of  claim 3 , further comprising, prior to step (a), isolating the cell from an individual. 
     
     
       5. The method of  claim 4 , wherein the cell is isolated from the patient. 
     
     
       6. The method of  claim 5 , wherein the cell is isolated from a donor individual different from the patient. 
     
     
       7. The method of  claim 3 , wherein the T cell is a tumor-infiltrating T lymphocyte, a CD4+ T cell, or a CD8+ T cell. 
     
     
       8. The method of  claim 1 , wherein the antibody or fragment therefor further comprises a heavy chain constant region, a light chain constant region, an Fc region, or the combination thereof. 
     
     
       9. The method of  claim 1 , wherein the antibody or fragment thereof is humanized. 
     
     
       10. A method of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of an antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human Programmed death-ligand 1 (PD-L1) protein and comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 7-26 and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 27-33. 
     
     
       11. The method of  claim 10 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 20 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 28.